Patients' experiences of the decision‐making process for clinical trial participation

Abstract Clinical decision‐making about participating in a clinical trial is a complex process influenced by overwhelming information about prognosis, disease, and treatment options. The study aimed to explore patients' experiences of the decision‐making process when patients are presented with the opportunity to participate in a cancer clinical trial and to shed light on how patients experience the health communication, the nurse's role, and the physician's role. A qualitative study design was applied. Nine patients with advanced cancer were interviewed after being informed about their treatment options. Data were analyzed using thematic analysis. The results showed that patients made treatment decisions mainly guided by their emotions and trust in the physician. Furthermore, the physicians had a great impact on the decisions, and the nurse's role was associated with conversations about how to manage life. The study highlights the importance of talking about prognosis and addressing the patient's existential issues, particularly in this context of advanced cancer. The study elucidates a need for healthcare professionals to engage in health communication about life when it is coming to an end.


| INTRODUCTION
Advances in cancer treatment are founded on research that tests new drugs and methods. One of the final stages of this long research process is the oncology clinical trial. In the first phases of these trials, new treatments are tested to determine whether they cause any serious harm, whereas the main purpose of the later phases is to explore the risks and benefits of the new treatment and to determine whether the experimental treatment is better than the standard treatment (National Institutes of Health, 2018).
To protect patients and ensure reliable study results, clinical trials follow strict scientific procedures. One of these procedures is informed consent (Emanuel et al., 2000;WMA, 2013), which aims to inform patients about the research and provide them with voluntary consent to participate in a clinical trial. Healthcare professionals are responsible for ensuring that patients understand the purpose, the procedures, and the potential harms and benefits of their involvement in the trial, and not least of all, the alternatives to participation.
Clinical trials provide both oral and written information and entail a complex and time-demanding consent process guided by ethical principles to protect the patients involved (World Medical Association, 2013). Decisions about participating in a clinical trial can be particularly difficult because patients will have to choose between a well-known and accepted standard treatment and experimental treatment whose treatment efficacy and side effects are less documented and might influence the patients' quality of life (Joseph-Williams et al., 2014;Mills et al., 2006). Furthermore, this decision-making process takes place at a time when the cancer patient and their relatives are in a highly vulnerable situation because of the life-threatening nature of the disease (Schaeffer et al., 1996).
The vast majority of research studies have focused on either recruitment or improving consent information in relation to trial participation. Moreover, most studies on patients' experiences about clinical trial decision-making have been conducted in curative settings, whereas less focus has been on the palliative setting where the cancer is advanced and a cure is no longer possible.
Existing research on clinical trial decision-making in the context of advanced cancer shows that the desire for curative treatment is the patients' primary motivation for clinical trial participation (Godskesen et al., 2013;Kvale et al., 2010) and that many patients are willing to try anything to achieve this (Harrop, Noble, et al., 2016;Kohara & Inoue, 2010) despite having been informed that the cancer is incurable. The research literature also indicates that patients are aware that they can decline further treatment but they tend to think that their life situation gives them no other choice than to opt for treatment in a clinical trial when offered participation (Moore, 2001).
These findings indicate the complexity of the decision-making process and that many patients with advanced cancer also feel overloaded with information provided by the healthcare professionals at a difficult and emotional time in life (Harrop, Kelly, et al., 2016;Shannon-Dorcy & Drevdahl, 2011). However, little is known about the patients' experiences with regard to the decision-making process.

| Aim
This study aimed to explore patients' experiences of the decisionmaking process when presented with the opportunity to participate in a cancer clinical trial. The research questions were: 1. How do patients experience the conversation with the healthcare professionals?
2. How do patients experience the role of physicians and nurses in the consultation?
3. How do patients experience the decision-making process? 2 | METHODS

| Data collection
Patients' experiences were explored through semistructured, in-depth interviews inspired by Kvale and Brinkmann (Kvale & Brinkmann, 2014) and data were analyzed using thematic analysis inspired by Braun and Clarke (Braun & Clarke, 2006). This study is part of a larger study in which additional data are collected through participant observations of a clinical outpatient setting where trial decisions are made.
Patients were recruited at a public university hospital in Denmark at the Department of Oncology from July 2016 to May 2019. The patient population included were all patients with advanced cancer offered to participate in a clinical trial. A total of 20 patients were approached for study participation and nine patients were interviewed, eight women and one man (Table 1). Before the interview, all patients had already received a consultation with an oncologist and an oncology nurse where they were informed about the cancer having progressed despite current treatment. During the same consultation, the patients were informed about new treatment options, including the possibility of participating in a clinical trial.
The interviews took place the same day as the consultation and up to 22 days after the consultation where the patients were informed about the clinical trial, most commonly within 2 weeks from the consultation. The interviews lasted between half an hour and 2 h and took place at the patients' home or the hospital, depending on each patient's wishes. Three patients preferred a telephone interview.
An interview guide was developed by the first author in cooperation with two of the coauthors, based on participant observation, knowledge of the field, and review of the literature. The interview guide contained open-ended questions and adjustments to the guide were made after discussions with the coauthors before and after interviews. All interviews were performed by the first author, recorded, and transcribed verbatim.

| Analysis
Applying thematic analysis, we searched to discover patterns and characteristics in the interview transcripts using an ongoing iterative process that followed six overall phases of the analysis, inspired by Braun and Clarke (Braun & Clarke, 2006).

Reading and rereading the interview transcripts to become familiar
with the data and to achieve a general understanding of the data. 6. Writing up the results, going beyond the description of the themes, and contextualizing the analysis in relation to existing research literature and relevant theoretical perspectives (which will be unfolded in the discussion section).

| Ethical considerations
The study was approved by the Danish Data Protection Agency through the Region of Southern Denmark. According to Danish law, interview studies do not need ethical approval; however, the Regional Scientific Ethical Committees for Southern Denmark was notified.
Patients and relatives provided verbal and written informed consent and were informed about their right to withdraw consent.

| Rigor
To ensure transparency (Kvale & Brinkmann, 2014), a detailed description of the participants, setting, data collection, and transcribing of data are described in the methods section. The six phases of the analysis are specifically outlined to ensure transparency throughout the data analysis. The study findings were evaluated through validation discussions with coauthors and fellow researchers which occurred throughout the whole data generating process, analysis, and presentation of findings. In this way, the reflections ensured coherence between interviews and interpretation (Kvale & Brinkmann, 2014).

| RESULTS
Four themes were identified and presented in Table 2, which also shows examples of codes leading to the themes. Each theme is described and illustrated with quotes from the interviews.

| Specific expectations regarding physician's role and nurse's role
It appeared from the interviews that the patients had very specific expectations regarding the respective roles of the physician and the nurse, and they experienced that the physicians and nurses contributed to separate parts of the conversations. doctors had the time for anything else than to send me further on with some medicine and chemo.
Other patients described how they were fishing for answers about life expectancy and how they tried to ask about prognosis and time left to live. These patients felt that they did not get the answer they wanted at the consultations and experienced that the most frustrating thing about the conversations was not getting a result. To go further into these statements, one patient said: That's the one thing they can't tell us, whether I'll become cancer-free. Another patient said: I also think, should I ask? I think it is his job too to say how the next course of disease might look, while one of the other patients talked a great deal about the things that had remained unsaid: That part… the unmentioned part… maybe that part about how big the chance is that I'll survive this.
That's what makes it tough.
Relational aspects were of great importance for the patients in the decision-making process. Most patients considered the physician to be the expert in the decision-making and relied on the physician's competences. Moreover, in talking about the nurses' role in general, several of the patients' statements reflected that they experienced conversations with the nurse to focus more on them as a person and not a patient.
As an example, one of the patients said: When you get such a message, you can't think of anything else … at a time like that, you should have half an hour with a nurse where the focus was only on me.

| Information overload in a vulnerable situation
The patients expressed satisfaction with the information they received and described both the oral and written information as being thorough and exhaustive. However, several patients expressed that they received too much information, especially referring to oral infor-

| When clinical trial information takes center stage
Some of the patients were referred from other hospitals for a specific experimental treatment that was not offered at their district hospital. This meant these particular patients experienced the information as being isolated from the context of having advanced cancer, and they reported that they did not experience that their lives as patients were taken into account. These experiences were not to the same extent shared by the patients whose decision-making about experimental treatment took place at their local district hospital.

| DISCUSSION
The  (Gregersen et al., 2019). Moreover, other studies show that being in treatment can be a way for patients to manage the feeling of fear when having cancer and a way to enable hope (Godskesen et al., 2013;Quinn et al., 2012). Accordingly, patients have described how the feeling of having influence on the treatment they receive is experienced as a way to gain control over their disease management (Quinn et al., 2011). Moreover, our findings revealed that the patients Regarding the role of the physicians, our findings showed that physicians had a great impact on treatment decisions. This is in line with other research studies describing the substantial role of the physician in treatment decision-making, which revealed that physicians make preformed decisions without the patients (Ofstad et al., 2014;Salloch et al., 2014) and that patients make decisions based on trust in the physician (Dellson et al., 2018) when physicians make recommendations for treatment (Eggly et al., 2008). Moreover, McCullough et al. (McCullough et al., 2010) found that physicians freely described their own role in treatment decision-making. In our study, some patients experienced that physicians initiated a talk about existential issues and life coming to an end, probably in order to support the patients in deciding which treatment to choose or whether they prefer not having any treatment at all. However, one of the challenges seemed to be that not all patients were prepared to or interested in talking about their own death and the feelings related to this. Our findings substan- preferences (Pluut, 2016;Silverman et al., 2013;Street et al., 2009).
Furthermore, in this context of advanced cancer, communication about cure should not be the pivot of the encounter, and patients may benefit from communication that focuses more on healing than on cure (Hutchinson, 2011). Healing has been described as a transition from anxiety and suffering toward a sense of integrity, completeness, and inner peace. This process requires more conscious communication, with a focus on relational and nonverbal communication. These are skills that must be learned individually by encouraging healthcare professionals to focus more on professional development within existential issues by, for example, offering training that includes reflection on the healthcare professionals 'feelings and reactions so that they can apply them when caring for the patient (Hutchinson, 2011). This requires systematic training in areas such as active listening, selfreflection, and awareness of their own nonverbal language, etc. (Krasner et al., 2009;McCormack et al., 2017). These are skills that are essential from the very first step in the decision-making process, which is to address the patients' emotions.
Our findings showed that patients particularly experienced that the whole situation seemed to be addressing them as a patient and less as a person, which came to light when the patients described how the decision-making process seemed to focus on treatment -

| CONCLUSIONS
The study shows that patients with advanced cancer made trial decisions based more on emotions than facts. The decisions about receiving experimental treatment were often based on fear, hope for a cure, and the feeling of having no real choice. The role of the physician had a great impact on the decisions because patients entrusted the decisions to the physician, who also influenced the decisions by the way he/she talked with the patients about their course of disease. The role of the nurse was associated with more existential aspects of life. In the context of advanced cancer, where the effect of the treatment is uncertain and not curative, the decision to participate did not represent all the patient's needs. Dialogue on prognosis and thoughts about how to live life when it is coming to an end should be considered as an important aspect of the decision-making process.

ACKNOWLEDGMENTS
We thank the patients, their relatives, and the healthcare professionals at the Department of Oncology for participating in our study.
This research paper is a part of a PhD project funded by Region of Southern Denmark and Lillebaelt Hospital, University Hospital of Southern Denmark, Denmark.

AUTHOR CONTRIBUTION
TAG has made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data and drafting the manuscript. RB and JA have made substantial contributions to conception and design, analysis and interpretation of data and been involved in drafting the manuscript and critically revising it. MW and KDS have been involved in drafting the manuscript and critically revising it.

CONFLICT OF INTEREST
None declared.

DATA AVAILABILITY STATEMENT
Data sharing not available due to informant anonymity.